The National Osteoporosis Foundation recently released new data estimating that approximately 9 million adults in the U.S. have osteoporosis, and more than 48 million have low bone mass placing them at increased risk for osteoporosis and bone fractures. Fracture risk associated with osteoporosis will become more serious as the nation's population ages. The FDA has approved a number of drugs designed to slow or reverse osteoporosis. The standard technique for diagnosing osteoporosis, and for monitoring pharmacological treatment, is Dual Energy X-ray Absorptiometry (DXA). DXA provides a measure of bone mineral density (BMD) which relates to bone quantity. Ultrasonic techniques may provide useful information about bone quality. Unlike x-rays which are sensitive mainly to bone density, ultrasonic waves are sensitive to microstructure and orientation which influence fracture risk. Even small changes in microstructure that do not affect overall bone mass are known to have a significant impact on the structural competence of bone. Ultrasonic devices called bone sonometers are becoming increasingly common as screening tools for osteoporosis. These devices offer advantages compared to DXA such as lower cost, better portability and no use of ionizing radiation. In spite of their potential, however, bone sonometers have not been shown to yield improved diagnostic information compared to that provided by DXA. In addition, bone sonometers in current clinical use do not produce diagnostic images, and cannot perform measurements at central skeletal locations such as the hip and spine where most osteoporotic fractures occur. The objective of our proposed research is to develop a new approach called the Backscatter Difference Technique that measures the difference in power between two different portions of an ultrasonic backscatter signal from bone. The technique uses a single transducer which improves access to central skeletal sites, and is adaptable to ultrasonic imaging systems. The technique also may be relatively insensitive to errors caused by intervening tissues. To achieve this objective, we have identified the following Specific Aims: 1) Refine and evaluate the Backscatter Difference Technique through in vitro measurements of human bone using a laboratory based ultrasonic measurement system; and 2) Adapt the Backscatter Difference Technique of ultrasonic bone assessment to imaging systems that are in widespread clinical use, but normally used to image soft tissues. A successful outcome to the proposed research will provide a means to assess bone quality and bone quantity at clinically interesting skeletal sites such as the hip and spine using technology that is available in ultrasonic imaging devices.